An information theory approach to stock market liquidity.

A novel methodology is introduced to dynamically analyze the complex scaling behavior of financial data across various investment horizons. This approach comprises two steps: (a) the application of a distribution-based method for the estimation of time-varying self-similarity matrices. These matrices consist of entries that represent the scaling parameters relating pairs of distributions of price changes constructed for different temporal scales (or investment horizons); (b) the utilization of information theory, specifically the Normalized Compression Distance, to quantify the relative complexity and ascertain the similarities between pairs of self-similarity matrices. Through this methodology, distinct patterns can be identified and they may delineate the levels and the composition of market liquidity. An application to the U.S. stock index S&P500 shows the effectiveness of the proposed methodology.

Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives.

Targeting the ubiquitin-proteasome pathway has emerged as a rational approach in the treatment of human cancer. Based on positive preclinical and clinical studies, bortezomib was subsequently approved for the clinical use as a front-line treatment for newly diagnosed multiple myeloma patients and for the treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma, for which this drug has become the staple of treatment. The approval of bortezomib by the US Food and Drug Administration (FDA) represented a significant milestone as the first proteasome inhibitor to be implemented in the treatment of malignant disease. Bortezomib has shown a positive clinical benefit either alone or as a part of combination therapy to induce chemo-/radio-sensitization or overcome drug resistance. One of the major mechanisms of bortezomib associated with its anticancer activity is through upregulation of NOXA, which is a proapoptotic protein, and NOXA may interact with the anti-apoptotic proteins of Bcl-2 subfamily Bcl-X(L) and Bcl-2, and result in apoptotic cell death in malignant cells. Another important mechanism of bortezomib is through suppression of the NF-κB signaling pathway resulting in the down-regulation of its anti-apoptotic target genes. Although the majority of success achieved with bortezomib has been in hematological malignancies, its effect toward solid tumors has been less than encouraging. Additionally, the widespread clinical use of bortezomib continues to be hampered by the appearance of dose-limiting toxicities, drug-resistance and interference by some natural compounds. These findings could help guide physicians in refining the clinical use of bortezomib, and encourage basic scientists to generate next generation proteasome inhibitors that broaden the spectrum of efficacy and produce a more durable clinical response in cancer patients. Other desirable applications for the use of proteasome inhibitors include the development of inhibitors against specific E3 ligases, which act at an early step in the ubiquitin-proteasome pathway, and the discovery of less toxic and novel proteasome inhibitors from natural products and traditional medicines, which may provide more viable drug candidates for cancer chemoprevention and the treatment of cancer patients in the future.

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Bioelectric impedance overestimates the body fat in overweight and underestimates in Brazilian obese women: a comparison with Segal equation 1.

INTRODUCTION: Overweight and obesity are risk factors to appearance of cardiovascular diseases and anthropometry is important as clinical tool for planning and health policymaking at population level. Thus, aim of this work was to compare the simple body fat percentage (%BF) obtained straight by bioeletric impedance (BIA) to the one obtained by the equation of Segal et al (1988), which uses the BIA resistance value, overweight among adult women. METHODS: This study conducted with 86 adult women (50.5±11.0 years old). Body weight and height were measured and estimated the body mass index (BMI). %BF was assessed by BIA (Biodynamics® model 450) and Segal equation. RESULTS: %BF derived from BIA (38.0±4.6%) and Segal et al (1988) (38.7±8.1%) were similar (p=0.85). However, when the women were distributed, in two groups based on their BMI, overweight (n=40; BMI=27.3±1.2 kg/m²) and obesity (n=46; BMI= 36.2±5.1 kg/m²), the two methods presented results significant different (p=0.000). The %BF of overweight women was 34.6±3.6% by BIA and 30.3±2.1% when estimated by Segal equation. In obese women, the %BF was 41.0±3.0% and 46.0±2.6%, respectively. CONCLUSION: BIA overestimated %BF in overweight (+14.2%; +3.0 kg) and underestimated in obese (-10.9%;-4.4 kg) women.

Eating disorders and aggressiveness among adolescents.

OBJECTIVE: To explore the links between propensity to aggression and eating disorders in a sample of school-aged adolescents in a northeastern area of Italy. METHOD: In a mixed male-female sample of 1000 adolescents (10% of the district's population aged 15-19 years) we administered the Eating Attitudes Test, the Bulimic Investigatory Test of Edinburgh and the Body Attitudes Test, as measures of abnormal eating attitudes and behaviours, and the Aggression Questionnaire, as a measure of the propensity to aggression. RESULTS: Females scored significantly higher than males at all eating disorders inventories (P < 0.0001). Males scored higher than females at the Aggression Questionnaire. In both genders, there was a positive correlation between scores at any of the eating disorders inventories and those at the Aggression Questionnaire (P < 0.0001). CONCLUSION: Overtly expressed aggression might have a negative impact on the course of eating disorders and on the compliance with treatment, also enhancing the risk of suicide.

Social desirability and eating disorders. A community study of an Italian school-aged sample.

OBJECTIVE: To explore the links between social desirability and eating disorders in a sample of adolescents in a north-east area of Italy. METHOD: A mixed male-female sample of 1000 school-aged adolescents, corresponding to 10% of the young population aged 15-19 years living in the district, were investigated with self-reported questionnaires, including the Eating Attitudes Test (EAT), the Bulimic Investigatory Test of Edinburgh (BITE), the Body Attitudes Questionnaire (BAT), and an Italian version of the Marlowe-Crowne Social Desirability Scale (MC-SDS). RESULTS: Females scored higher than males at all eating disorder inventories. In both genders there was a negative relationship (in all cases P < 0.01) between scores at the eating disorder inventories and those at the MC-SDS. When analysing eating disorder "caseness", as measured by cut-off, "cases" reported significantly lower scores than "non-cases" at the MC-SDS in both genders. CONCLUSION: Personality traits measured by the MC-SDS, such as defensiveness, self-esteem, and dependence from approval, might contribute to the development of abnormal eating patterns at risk of eating disorders.

The histopathology of non-steroidal anti-inflammatory drug induced gastroduodenal damage: correlation with Helicobacter pylori, ulcers, and haemorrhagic events.

AIMS: The spectrum of microscopic lesions resulting from the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), known as chemical gastritis, remains unclear, and the variable prevalence reported in different studies makes this issue a matter of lively debate. The aim of this study was to evaluate the prevalence and importance of chemical gastritis in patients regularly taking NSAIDs. Owing to the high prevalence of Helicobacter pylori infection, particularly in subjects over 60 years of age, and in view of a possible association with damage, the presence of H pylori infection in the same tissue sample was also determined in all patients. METHODS: One hundred and ninety seven subjects were enrolled, 118 of whom were receiving chronic treatment with NSAIDs and 79 of whom were controls, pair matched for age, sex, and clinical symptoms (ulcer-like dyspepsia or upper digestive tract haemorrhage). Antral biopsies taken during upper gastroduodenal endoscopy were assessed for chemical gastritis according to a modified version of Dixon's score, and for Helicobacter correlated chronic active gastritis, according to the updated Sydney system. RESULTS: Chemical gastritis was identified in 11 patients taking NSAIDs (9%) and in four controls (5%) (p < 0.05). Helicobacter pylori was detected in 53 patients taking NSAIDs (45%) and in 34 controls (43%). Patients taking NSAIDs had a significantly higher number of erosions and ulcers and worse endoscores than controls. The presence of H pylori did not appear to increase histological damage, ulcer prevalence, or haemorrhagic events. CONCLUSIONS: Chemical gastritis is present in a limited number of patients regularly taking NSAIDs, and is not strongly correlated with NSAID induced damage. In many cases of peptic ulcer or upper gastrointestinal bleeding in patients taking NSAIDs, the presence of chemical gastritis or H pylori infection cannot solely account for the development of mucosal damage.

Gastrectomy, lack of gastric first pass metabolism of ethanol and alcoholic liver disease. Results of a multicentre study.

BACKGROUND: Some conditions characterized by a loss (anatomical or functional) of parietal cells of the gastric antrum, containing an alcohol-dehydrogenase, may reduce the first pass metabolism of ethanol at that level and, simultaneously, raise its bioavailability. The observation that the first pass metabolism was drastically suppressed after gastrectomy would appear to suggest that the latter condition represents a risk for the development of liver damage in patients who continue to consume alcohol even in a non relevant amount. METHODS: Consecutively enrolled in the study were 304 individuals of both sexes aged between 45 and 70 years of whom 114 gastrectomized and 190 pair-matched control subjects all submitted to an Upper Gastrointestinal Endoscopy for whatever disturbance. All the patients were diagnosed as having liver disease with routine clinical and instrumental means. Information was collected concerning the mean daily alcohol intake, both before and after the operation. RESULTS: The overall prevalence of hepatic lesions was shown to be higher in the gastrectomized than in the control group (42.1% vs 25.8%, p = 0.005). Moreover, referring only to alcohol-related hepatic lesions (steatosis, steato-fibrosis and cirrhosis), the prevalence was higher in the gastrectomized patients than in the controls (29.8% vs 17.9%, p = 0.02). As far as concerns alcohol consumption, the gastrectomized group had consumed 71 g/day and the control group 39 g/day alcohol per person (p < 0.05) in a similar period of time (35 and 33 years, respectively). Also the non alcohol-related liver damage (especially the viral type) was slightly higher in the gastrectomized patients (gastrectomized 12.3% vs control 7.9%, p = ns). Accordingly, the percentage of serum markers of viral infection was higher in this group (HBs Ag: gastrectomized 3.9% vs control 2.2%, p = ns; anti-HCV: gastrectomized 13.5% vs control 5.0%, p = 0.03). Finally, to test the eventual damaging effects of gastrectomy alone (excluding ethanol and/or viral infection), two groups of patients with a medium to low alcoholic negative assumption (30-60 g ethanol/day) and no signs of viral infection (HBsAg and anti-HCV negative) were extrapolated. In these two selected groups, the prevalence of alcoholic-related hepatic lesions were not statistically different (28 gastrectomized 20.3% vs 44 control 18.4%). CONCLUSIONS: In conclusion, data emerging from investigations on the population under study indicate that the alcohol and viral infection appear to play a more important role in determining hepatic lesions than gastroresection.

[Emergencies in colorectal diseases: role of the endoscopist]. / Le urgenze nella patologia del colon-retto: il ruolo dell'endoscopista.

In some emergency situations of colo-rectal pathology, especially those characterized by hemorrhaging, the endoscopy has acquired, with the passing of years, a fundamental role both from the diagnostic and the therapeutic point of view. In no more than 25% of the lower intestinal tract hemorrhages, the clinical picture does have the signs of an emergency. The diverticula, IBD and angiodysplasias are primarily responsible for rendering these characteristics. Even when possible problems concerning an accurate intestinal cleaning can arise, a correct diagnosis is possible at least in seven cases out ten. When the colonoscopy isn't conclusive and the bleeding persists may be recommended the selective arteriography (helpful also in hemorrhages lower than 0.5 ml/min). Also in cases of acute obstructive syndrome the colonoscopy, taking advantage of the direct view of the lesion, can give a correct diagnosis, sometimes supported by the histologic examination. Regarding the operating capacity of the method, the endoscopy can resolve minute and localized bleeding lesions. The Argon or Nd:YAG laser photocoagulation is widely used. Recently BICAP and heater probe methods have been developed, which aveld the problem connected to the HF electrocoagulation. A very efficacious and simple method is that of injecting 1:10.000 adrenalin, 1% polidocanol, absolute ethanol or hypertonic solution around the lesion. The scarred strictures are those more easily and safely treated by pneumatic dilatation or (limited to the rectum-sigmoid) by Savary sounds. In the volvulus or bowel invagination, just by having the endoscope goes up in the lumen, often normal condition settles again. In the Ogilvie's syndrome you can deflate the cecum with an aspirator or more simply by positioning a tube above the hepatic flexure, with 85% success. In the malignant strictures the debulking of tumor mass by laser treatment, sometimes followed by dilatation, may be preparatory to the surgery or purely palliative. Finally the extraction of foreign bodies must be performed, in order to obtain a relaxed anal sphincter, in general anaesthesia or by a previous rigid rectoscope dilatation.

Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. The TriVeneto Viral Hepatitis Group.

Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis C, but only 20% to 30% of patients are apparently cured with the current recommended schedule of 3 MU given three times a week for 6 months. To evaluate the efficacy of more aggressive treatment regimens, we have conducted a randomized trial in 174 patients with chronic hepatitis C using three different schedules: (1) 12-month treatment starting with 6 MU/ three times a week and decreasing the dose on the basis of serum alanine transaminase (ALT) activities (group A: 59 cases); (2) fixed dose of 3 MU three times a week for 12 months (Group B: 61 cases), (3) fixed dose of 6 MU three times of week for 6 months (Group C: 54 cases). Patients were evaluated during therapy for biochemical and virological response and followed for at least 12 months after therapy to assess long-term efficacy and liver histological outcome. The genotype of infecting HCV was also analyzed in all patients, and predictors of response were determined by multivariate analysis. Serum ALT became normal during therapy in 76% of patients (95% confidence interval [CI]: 63 to 86), 65% (CI: 52 to 77), and 74% (CI: 60 to 85) in groups A, B, and C, respectively (P = NS). The corresponding figures for sustained response 12 months after therapy were 49% (CI: 36 to 62), 31% (CI: 20 to 44), and 28% (CI: 16 to 42)(A vs. B, P = .06; A vs. C, P = 0.03). Eighty-six percent of patients with sustained response cleared HCV-RNA from serum, and 72% improved histologically.(ABSTRACT TRUNCATED AT 250 WORDS)

[A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. / Metanalisi dei trial terapeutici con ademetionina nel trattamento della colestasi intraepatica.

S-adenosyl-L-methionine (ademethionine) has been recently proposed as a therapeutic agent for the treatment of intrahepatic cholestasis (IHC), a syndrome that overlaps with many different types of liver diseases. To obtain a global assessment of the results of the therapeutic efficacy of this compound, a meta-analysis of 6 controlled clinical trials with ademethionine in the symptomatic treatment of IHC of liver diseases and pregnancy was carried out. The therapeutic response to ademethionine treatment, for 15 to 30 days, proved to be superior to placebo, as assessed by resolution of pruritus, normalisation or 50% improvement in serum total bilirubin, serum conjugated bilirubin, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. At present, the therapeutic effect of ademethionine should be regarded as symptomatic, but long term studies on the effect of drug administration on the course of the disease and survival are being performed.

Patterns of antibodies to hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication and liver disease.

Patients with hepatitis C virus infection may have circulating antibodies to various structural and nonstructural antigens of the virus. To assess whether the antibody profile is related to epidemiological or clinical features of chronic infection or to viral replication, sera from 172 consecutive patients with biopsy-proven chronic non-A, non-B hepatitis were studied for antibodies to nonstructural and structural hepatitis C virus antigens and for serum hepatitis C virus RNA with the polymerase chain reaction using primers derived from the 5' noncoding region. Three subgroups could be identified on the basis of their seroreactivity to hepatitis C virus: 133 cases (77.3% [group A]) were positive on first- and second-generation assays and had antibodies to C100-3 and to C22, C33c or both identified on recombinant immunoblot assay; 23 cases (13.4% [group B]) were positive only on second-generation assay and reacted with C22, C33c or both but not with C100-3; and 26 cases (9.3% [group C]) were negative for all hepatitis C virus antibodies. Mean age and sex distributions were similar among the three groups; a history of transfusion was more frequent among cases in group B (p = 0.06). These patients also had the highest serum aminotransferase values (p = 0.001). Liver histological studies showed active necroinflammatory changes in 69.2% of patients in group A and 52.2% of those in group B but only in 25% of cases in group C. Serum hepatitis C virus RNA was frequently detected in patients of groups A and B, independent of their recombinant immunoblot assay profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. The TVVH Study Group.

Two hundred and thirty-four patients with chronic non-A, non-B hepatitis, 86% positive for anti-HCV by ELISA, were treated with recombinant interferon-alpha 2a or with natural (human-leukocytes-derived) interferon-alpha using different dosage and periods of administration. Interim analysis of follow-up data indicate that 65-70% of patients treated initially with 6 MU, thrice weekly, of recombinant interferon-alpha 2a achieved a complete biochemical response (normalization of alanine aminotransferase: ALT) during therapy compared to 56-58% of those treated with 3 MU, thrice weekly, of recombinant or natural interferon-alpha. A 12-month schedule of interferon administration appeared superior to a 6-month schedule in reducing the probability of reactivation of liver disease after therapy withdrawal, although further data are needed to confirm such a conclusion. The probability of response to interferon in terms of maintaining normal ALT after withdrawal did not appear to be influenced by sex, while it was significantly higher in patients aged below 45 years and in those without cirrhosis.

[S-adenosyl-L-methionine (SAMe) and its use in hepatology]. / L'S-adenosil-L-metionina (SAMe) e il suo uso in epatologia.

S-adenosyl-L-methionine (SAMe), a molecule naturally present in several body tissues and fluids, is produced, by SAMe synthetase, from ATP and methionine. SAMe has a fundamental role, as methyl group donor, in transmethylation reactions in which the synthesis of membrane phospholipids (especially phosphatidylcholine) is mandatory for the maintenance of membrane fluidity. Another metabolic pathway involving SAMe, transsulphuration, is initiated with the release of -CH3 from the molecule and the formation of S-Adenosyl-homocysteine and then homocysteine and cysteine, a precursor of glutathione the main cellular antioxidant, responsible of detoxification of various compounds and xenobiotics. At last SAMe is implicated in aminopropylation process for the polyamine synthesis. The development of stable double salt of p-toluene sulphonic acid and sulphuric acid of SAMe enables the clinical use of the drug, as a therapeutical agent, for the treatment of a number of liver dysfunctions. In various animal and human models, including controlled trials, it has been demonstrated that SAMe can ameliorate some biochemical parameters and pruritus in cholestasis induced by a range of compounds (i.e. oestrogens, lithocolate, etc) and in intrahepatic cholestasis superimposed to chronic liver disease. Concerning alcohol toxicity, SAMe prevents, in ethanol fed baboons, depletion of glutathione levels, normalizes the mitochondrial enzymes and improves the histological hepatic lesions. In human healthy volunteers it has been recently demonstrated that SAMe, after ethanol ingestion, significantly lowers plasma concentration of ethanol and acetaldehyde as well. Finally, SAMe has been proposed, instead of N-acetylcysteine, as precursor of glutathione, in patients who present late after ingestion of an overdose of paracetamol.

Effects of ranitidine on blood alcohol levels after ethanol ingestion. Comparison with other H2-receptor antagonists.

OBJECTIVE: To determine whether the H2-receptor antagonist, ranitidine, which is a potent inhibitor of gastric alcohol dehydrogenase activity in vitro, increases the bioavailability of orally administered ethanol (0.3 g/kg of body weight) and to compare the resulting blood alcohol concentrations with those of two other H2-antagonists, cimetidine and famotidine, the latter of which does not inhibit gastric alcohol dehydrogenase. DESIGN: For each of the H2-receptor antagonists, a different group of subjects was used. In each group, a paired design was adopted with each subject serving as his own control. SETTING: Hospital laboratory. SUBJECTS: Normal, healthy men aged 24 to 46 years. INTERVENTION: Eight men were treated for 1 week with ranitidine (300 mg/d), six with cimetidine (1000 mg/d), and six with famotidine (40 mg/d). MEASURES: Peak blood alcohol concentrations, areas under the blood alcohol curve, first-pass metabolism, and bioavailability of orally consumed ethanol. RESULTS: Relative to baseline, ranitidine increased the mean peak concentration and the area under the curve of blood alcohol concentrations by 34% (P less than .05) and 41% (P less than .01), respectively. First-pass metabolism of ethanol was decreased from 70 +/- 10 to 31 +/- 9 mg/kg of body weight, with a corresponding increase in ethanol bioavailability of 79.6% to 92.6%. By comparison, cimetidine had even a greater effect on blood alcohol levels, while famotidine had no significant effects. CONCLUSION: Patients treated with ranitidine or cimetidine should be warned of possible functional impairments after consumption of amounts of ethanol considered safe in the absence of such therapy.

S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.

Previous studies have shown that S-adenosylmethionine (SAMe) counteracts oestrogen-induced bile secretion failure. In order to confirm this anticholestatic activity, we conducted a single-blind clinical trial comparing SAMe with placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP). Thirty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (800 mg/day i.v.) or placebo until delivery for a mean period of 18 days. After SAMe, the women exhibited significantly (p less than 0.01) lower levels of total bile acids, serum conjugated bilirubin and aminotransferases with respect to pretreatment levels as well as to the corresponding values of the placebo group. In addition, SAMe significantly reduced pruritus whereas placebo was ineffective. No adverse reactions on mother or child were recorded during SAMe treatment, and the follow-up of these cases showed an incidence of premature labour (earlier than 37 weeks of gestation) in 2 out of 15 vs 5 out of 15 cases in the placebo group. In conclusion, these findings document that SAMe is more effective than placebo in ameliorating subjective and objective parameters of ICP.